In the 1998 World Youth Championships, Powell went 3 for 7 with a home run. In the final game against Taiwan, Powell entered as a pinch-hitter in the 7th and walked. The club was down 10-4 when the inning started, but Powell came up to bat again later in the inning and hit a two-out single that drove in Ruben Salazar with the winning run.

Powell was one of the top high school juniors in the USA in 2000, making the second team Baseball America All-American team after hitting .397 with 14 HR and 47 RBI in 78 AB. He led the team to the North Carolina 4-A Championship. Even more impressive, it was a rebound year as Powell had missed his sophomore season with injuries. Baseball America rated him the #2 high school prospect in America entering his senior year in 2001 but Powell got his GED in December and applied for the MLB 2000 amateur draft. With no teams realizing he was available, he was undrafted and became a free agent. The commissioner's office, though, placed a signing freeze on Powell until August 9, when he was freed from the hold. It was generally considered that the Powells wanted at least $3 million, equivalent to a high first-round choice. Landon's father Ron said two teams offered certain figures and the family agreed to both, but the clubs backed out - each saying they didn't want to be the team to get involved in the fiasco. Additionally, the involvement of Scott Boras in an advisory role made teams very cautious. Several agents claimed collusion was involved; MLB's collusion rules, though, only apply to major leaguers, and collusion is permitted for draftees. Powell returned to high school on August 29. Baseball America termed it the "most unique draft-related scenario" of the year.

Powell struggled as a freshman, hitting just .169/?/.338. He was the only freshman position player to see action on the #12 team in the country, impressive considering he was an early entry into college. In 2002, Powell batted .292/.350/.485 as the only sophomore position player on the #2 team nationwide. He went 2 for 4 with 2 runs, a double and an error in the final game of the 2002 College World Series and made the All-Conference team.

Powell had another fine year in college in 2004, hitting .328/.423/.612 with 19 homers, two behind teammate and SEC leader Steve Pearce. Landon was again an All-Conference pick at catcher. Powell was the #2 offensive threat on the #3 team in the nation, behind Pearce. Baseball America named him 2nd-team All-American, behind Kurt Suzuki and ahead of Chris Iannetta at catcher. Powell again starred in the CWS and made the 2004 College World Series All-Tournament team.

Assigned to the Vancouver Canadians, Powell hit .244/.368/.370 with 26 walks in 38 games. Baseball America ranked him as the #16 prospect in the Northwest League. He wasn't the highest-ranked catcher on his own team, though, as Kurt Suzuki was picked at #12.

On February 3, 2005, Landon severely injured his knee while doing drills. He needed potentially career-ending surgery and underwent 8 months of rehabilitation. He missed the entire season.

With Suzuki now at AA, Powell had fallen down the A's depth chart. Trying to bounce back in 2006, he hit .268/.333/.341 for the AZL Athletics and .264/.350/.439 for the Stockton Ports with 15 homers in 90 games. Baseball America rated him as the best defensive catcher in the California League. He led the league's catchers in fielding percentage (.994), putouts (611) and assists (69). Baseball America rated him the #15 prospect in the California League, between Ben Harrison and Yung-Chi Chen.

Powell made it to AA in 2007 with the Midland Rockhounds and played 4 games with the AAASacramento RiverCats. For the season, he hit a combined .292/.385/.525 in 64 games. He played 88 games for Sacramento in 2008, batting only .230 but with 15 home runs and 53 RBI.

In spring training of 2009, Landon Powell made the Oakland Athletics' roster to back-up Suzuki at catcher. He played his first game on April 11 facing Seattle and hit a two-run double in 4 at-bats, also coming in to score. He played in 46 games that first year, 36 as a catcher and 6 as a first baseman, and hit .229/.297/.429. The best part of his season was his 7 home runs in only 140 at bats. He returned in the same role in 2010, but hit even less - .214/.305/.304 in 41 games, playing catcher almost exclusively. In 2011, his batting line fell even further, to .171/.246/.225, good for an OPS+ of barely 32 - in 36 games as Suzuki's back-up. He spent brief periods of time at Sacramento in both 2010 and 2011, hitting .200 in 14 games the first year, and .283 in 12 games the second. On December 23, 2011, the A's designated him for assignment in order to clear a spot on their roster for Derek Norris, a catching prospect acquired the previous day in a trade with the Washington Nationals.